Vaccination is a critical veterinary practice for the purpose of protecting healthy animals from infectious diseases. The intent of vaccination is to stimulate a protective humoral and/or cellular immune response in healthy animals to targeted disease organisms. Though vaccination usually begins between 6-9 weeks-of-age, the first vaccination can be administered as early as 3-weeks-of-age. However, at younger ages vaccine efficacy is dependent on the presence and concentration of maternal antibody.
For dogs it is generally accepted that in properly vaccinated bitches the passive transfer of maternal antibody through the placenta and by ingestion of colostrum will protect puppies from certain infectious diseases. Passively derived antibody received from the mother may circulate in the puppy for as long as 20 weeks. However, the duration of passive protection is dependent on the half-life of the antibody and amount of antibody transferred. In general the half-life of canine IgG antibody is 11-14-days. The concept of vaccinating pregnant bitches to passively protect newborn puppies from disease due to canine herpes has recently been implemented commercially.
However, it has not been demonstrated that a multivalent, inactivated vaccine could be administered to bitchs for the specific purpose of eliciting immunologically effective amounts of maternal antibodies for transfer to at least one pup after whelping. Consequently, puppy vaccines are currently given as early as four weeks of age and then repeated every three to four weeks, until sometime after twenty weeks of age. However, there are situations where, due to the level of circulating maternal antibodies, vaccination may fail to protect against a field challenge.
A newborn puppy is born with essentially no antibodies of its' own. Furthermore, its immune system requires several months to be fully competent. At birth, initial protection from pathogens that puppies comes into contact with is by the presence of circulating antibody passively derived from its' mother.
During the first 2 days after giving birth mother's milk contains high levels of her own antibodies. This antibody laden milk is known as colostrum. A newborn pup must ingest colostrum during the first 24 hrs after birth to obtain protective antibodies from its mother. After 24 hours the pup's gastrointestinal tract becomes more mature and the absorption of intact antibody protein molecules ceases. Antibody that is not absorbed is digestion and is no longer absorbed as functional molecules and transferred to the circulation. The amount of antibody absorbed depends on the quantity of colostrum ingested and the level of maternal antibody in the colostrum. Nursing pups will obtain an adequate amount of antibodies during the first 24 hours after birth if the circulating antibody level is high in the bitch. Conversely, if the antibody level (low antibody titer) in the bitch is low as a result of remote vaccination or poor immune response, then pups will receive an insufficient level of antibody for passive protection. Both of these situations have positive and negative results. If maternal antibody levels are low, or pups ingest a minimal amount of colostrums, the passively transferred antibody in the pups may be metabolized before the first vaccination is administered and a period of susceptibility to disease will exist. On the other hand, if the level of maternally derived antibody is high at the time of first vaccination, an active immune response in the pups will be minimal. High maternal antibodies levels will neutralize vaccine antigens preventing stimulation of the immune system. However, until an active immune response can be initiated in the puppy, the danger of a serious infection increases as the passive antibody level wane over time. The only way to evaluate the situation in an individual pup is to determine antibody titers before vaccination. Such a practice is expensive and not readily available. A basic rule of thumb is to assume that from about age 4 weeks until 15 weeks pups may not be adequately protected and until active immunity can be established care should be taken to limit environmental exposure.
The age at which a pup becomes susceptible to infection is determined primarily by the passive antibody titer at the time of exposure. Pups born to seronegative bitches are susceptible at birth; pups from bitches with low antibody titers may be susceptible as early as four to six weeks after birth, whereas pups from bitches with high titers may be immune to infection for 12 to 16 weeks.4 
To increase the level of protection and/or the length of protection, pups can be immunized. However, common problem in vaccinating canines, such as dogs and puppies, is the maternal antibody interference during immunization. Maternal antibody interference is the most common cause of vaccine failure in weanling animals.1 Maternal antibody neutralizes vaccine virus and suppresses a pup's active immune response. This common immunization problem occurs with all diseases, but is of particular concern in the case of the CPV's enteritis because of the explosive nature of disease transmission and because pups are at greatest risk of CPV-induced mortality.
Pups receive about 10% of their CPV maternal antibody via transplacental transfer and the remaining 90% through colostral absorption during the first 24 hours after birth.3 At about three days of age, a pup's antibody titer usually equals that of its bitch. Because maternal antibody is not actively replaced, it declines at a predictable rate; a pup's titer falls by half about every 10 days or so.
Maternal CPV antibody would be much less problematic if pups remained protected from disease for as long as antibodies interfered with vaccination. However, there is a two-to five-week time period when antibody titers have declined so much that a pup is susceptible to virulent virus, but are still high enough to remain refractory to immunization with current vaccines.1 Vaccinations given before or during this time period will not stimulate active immunity in the pup. 5 
Further potential problems with vaccines include choosing an appropriate vaccine regiment. Of concern in any vaccine regiment is the choice of vaccine. As a basic matter, the choices will include univalent and multi or polyvalent vaccines. Univalent vaccine will immunize an animal against one single disease. Polyvalent or multivalent vaccines can immunize against several diseases. There are killed vaccines, live vaccines, and attenuated vaccines (modified live). Different vaccines are made in different ways. Each has a good reason for use and also potential problems. Univalent vaccines require multiple injections of different vaccines to make sure coverage for several diseases is given. Multivalent vaccines can overwhelm an immune system and cause immune suppression making the pup susceptible to minor infections or illnesses that would otherwise not affect him. Killed vaccines are not as effective in stimulating the immune system to make antibodies while modified-live (ML) vaccines reproduce in the animal's body and result in a higher antibody response. ML vaccines can also cause illness in the animal because they do reproduce and viruses are shed in feces or urine or saliva and bacteria are also shed until the animal is able to fight off the infection and kill the remaining organisms. Also ML vaccines can revert to the infective (virulent) form or even to a more virulent form and can contaminate the environment with viruses and bacteria that are infective to wild animals, birds, or even people. Vaccines which are made in chicken eggs can also stimulate the dog to be very allergic to eggs or chickens. Vaccines made in feline cell cultures can be fine the first time used and create a severe reaction the second shot because the dog may have made antibodies to the feline cells. Proteins from even the canine cell cultures can stimulate the pup to make antibodies that will attack it's own thyroid, adrenal, blood cells, nerve cells or essentially any of his own body tissues and result in mild to life threatening autoimmune diseases. The ML vaccines can contain undetected viruses gotten from the cell culture material that can also cause serious problems. [“A Brief Review of Canine Neonatal Immunology” found on the website of Versatility in Poodles, Inc. at http://web.foothill.net/vipoodle/neoim.htm.]
However, even with all these problems and/or difficulties, vaccination is recommended. The choice of vaccine regiments should be coordinated through a veterinarian and made on the basis of the specie of canine and/or other animal. [“A Brief Review of Canine Neonatal Immunology” found on the website of Versatility in Poodles, Inc. at http://web.foothill.net/vipoodle/neoim.htm.]
There is currently no all-killed multivalent vaccine on the market. Attempts have been made, but without success. The prior art discloses that multivalent vaccines are very difficult to manufacture an all-killed multivalent vaccine that will stimulate the immune system to make antibody against all the components equally. [See “A Brief Review of Canine Neonatal Immunology” found on the website of Versatility in Poodles, Inc. at http://web.foothill.net/vipoodle/neoim.htm.]
Some veterinary experts are recommending that after the first puppy immunizations the dog be tested for antibody level (titers) to see if they actually need a booster. Some dogs never need another booster, others need several boosters.
Accordingly, the art field is in search of an effective vaccine that protects pups without the attendant interference experienced from maternal antibodies, as explained above.
Of particular concern to young puppies are the diseases of Canine Rota Virus (CRV), Canine Herpesvirus (CHV), Minute Virus of Canines (MVC). Typically, a pups immnune system will grow and develop protection to these diseases within the first few months of life. Unfortunately, transmission of the disease to young pups can have detrimental effects on their condition and/or development. To further complicate, the problems associated with varying maternal antibody transfer to pups at whelp and effectiveness of that transfer make it difficult to assure vaccination of all pups in the whelp, even assuming that all pups consume an appropriate amount of colostrums.
Two distinct parvoviruses (CPV), are now known to infect dogs—the pathogenic CPV-2, which was recognized as a new disease of dogs and wild canines in 1978, and the “minute virus of canines” (MVC, CPV-1) reported by Binn in 1970. MVC, a completely different parvovinis, had not been associated with natural disease until 1992. MVC may cause pneumonia, myocarditis and enteritis in young pups, or transplacental infections in pregnant dams, with embryo resorptions and fetal death.
Information about Canine parvovirus (CPV and CPV-1) is available through most mediums. For instance, the website http://www.hagen.com/uk states that CPV is an acute, highly contagious, gastro enteritis of primarily young dogs (peak incidence of 6-20 weeks). Spread via the fecal-oral route and inanimate objects contaminated with infected feces can spread the virus because of its ability to survive long periods of time in the environment. Symptoms occur 5-10 days after exposure. Older animals tend to fight off clinical disease, unless they are immune compromised. However, young animals can be drastically affected.
Canine rotavirus (CRV) can be an important cause of diarrhea, especially in puppies less than twelve weeks of age. It is not common in puppies older than twelve weeks. Rotavirus is spread through feces of infected puppies. The most common symptom is diarrhea. Almost all puppies will be under twelve weeks of age and most will be two weeks of age and less. Most cases of diarrhea are relatively mild. However, some cases are fatal.
Most authorities do not consider canine rotavirus to be of major concern. This is because it is not commonly encountered and fatalities in normal puppies are rare. It should, however, be a consideration when puppies are encountered with diarrhea especially if around two weeks of age.
Canine herpes virus is another disease causing virus that primarily causes problems in younger puppies. The disease is generally asymptomatic in dogs infected when older than 1-2 weeks of age at the time of exposure. Disease caused by CHV is generally fatal in neonatal pups who lack immunity derived from their dams. The virus is usually transmitted due to poor animal husbandry conditions or shedding. See Carmichael, L. Neonatal Viral Infections of Pups: Canine Herpesvirus and Minute Virus of Canines (Canine Parvovirus-1). In: Carmichael L. (Ed.), “Recent Advances in Canine Infectious Diseases.” Ithaca: International Veterinary Information Service (www.ivis.org), 1999; document no. A0102.1199.
Pups rarely die if they are 2-3 weeks old at the time of exposure. The duration of illness in newborn pups is 1 to 3 days. Signs consist of anorexia, dyspnea, pain upon abdominal palpation, in coordination and, often, soft, yellow-green feces. There may be a serous, or hemorrhagic nasal discharge. Petechia are common on the mucous membranes. Rectal temperatures are not elevated. Thrombocytopenia has been reported in dying pups. CHV also may cause occasional in utero infections that result in the death of fetuses or pups shortly after birth. The virus also has been isolated rarely from dogs with vaginitis, conjunctivitis and respiratory illness. Asymtomatically infected dogs, or dams who suffered in utero infections, remain latently infected and virus may be excreted for about 1 week in nasal secretions or in genital secretions, and, thereafter, at unpredictable intervals over periods of several months, or years. See Carmichael, document no. A0102. 1199. Low maternal antibodies in the puppies are often the reason for a puppy contracting the virus.
Accordingly, the art field is in search of a vaccine regiment to protect pups from Canine Minute Virus, Canine Herpes Virus, and Canine Rotavirus after whelp and until the pups' immune system becomes more developed.